My patient has positive celiac disease serologies but is declining or cannot tolerate a biopsy to confirm celiac disease

**NOTE TO PROVIDERS REGARDING THIS SECTION: While other international societies such as the European Society for Pediatric Gastroenterology, Hepatology and Nutrition have published evidence-based guidelines^[1](#fhir-question-154e033da684832eef8780b02200886f)^ providing for diagnosis of celiac disease in children based upon serologic and clinical criteria alone, according to current NASPGHAN guidelines for the diagnosis of celiac disease^[2](#fhir-question-9a07d0cc3fa9e5ae3d6b34e018d666a1),[3](#fhir-question-9231a113a2544f625c3e0970bc3af532)^, the gold standard for celiac disease diagnosis remains a small bowel biopsy. Recognizing that many families may still decline this guidance, this section is intended to aid providers in better clarifying the diagnosis when biopsy data are not available. With the rare exception of those who may not tolerate the required procedure, a small bowel biopsy should be offered and recommended to all patients with possible or probable celiac disease prior to gluten exclusion.**

Is the patient symptomatic (may include abdominal pain, diarrhea, distension, anemia)?
A variety of symptoms may be associated with celiac disease, though it is to the provider’s discretion which are clear symptoms of celiac disease in a particular patient.

Yes, the patient is symptomatic

No, the patient is not symptomatic; testing was performed as a result of a screening protocol

Yes, the patient is symptomatic

Is the tissue transglutaminase IgA titer > 10 times the upper limit of the laboratory’s reference range (while the patient continued to consume unrestricted gluten)?

Yes, TTG-IgA was > 10 times the laboratory’s upper limit of normal

No, TTG-IgA was elevated but < than 10 times the upper limit of the laboratory’s reference range

### Yes
Meets criteria for a serologic diagnosis of celiac disease. While duodenal biopsy remains the gold standard for diagnosis of celiac disease, if symptoms improve with gluten withdrawal patients under these circumstances have a high probability of having celiac disease. Parents should nonetheless be advised as to potential drawbacks of forgoing a biopsy (missed additional conditions, potential adherence implications of the lack of biopsy confirmation, management dilemmas in the event that the symptoms return or do not completely dissipate). If symptoms do not subside with a gluten-free diet, the diagnosis should be explored further and biopsy should be seriously reconsidered.

### No
Does not meet criteria for a serologic diagnosis of celiac disease. Negative HLA typing despite the remaining compelling data casts tremendous doubt upon a diagnosis of celiac disease. The provider may wish to consider repeating serology at an alternative laboratory if there is any question as to the validity of the original results. Endoscopy must be considered to exclude other conditions such as inflammatory bowel disease which may trigger false positive celiac autoantibodies.

### No, an IgA endomysial antibody was not collected
While the patient continues to consume gluten, test for endomysial IgA antibody. If negative, the patient does not qualify for a non-biopsy diagnosis. If positive, proceed with HLA typing for DQ2 (DQA1\*05:01/05:05 and DQB1\*02:01/02:02) and DQ8 (DQA1\*05:01/05:05 OR DQB1\*02:01/02:02), one of which must be present to confirm a celiac disease diagnosis.

### No, TTG-IgA was elevated, but < than 10 times the upper limit of the laboratory’s reference range
Cannot make a serologic diagnosis of celiac disease. Would otherwise recommend biopsy for confirmation. Under circumstances where a biopsy is still declined despite thorough discussion, a gluten challenge (roughly 2 servings of gluten - e.g., 2 slices of wheat-based bread - daily for 6-8 weeks)^[4](#fhir-question-2bbe3f3e2bd385e5b274173883f2d6fb),[5](#fhir-question-2462a97b2734ca7331ad392530655051)^ should be considered for a later time point following treatment.

### No, my patient is IgA deficient and TTG-IgA is negative, and other markers (deamidated gliadin IgG, tissue transglutaminase IgG) are elevated
Cannot make a serologic diagnosis of celiac disease. Would otherwise recommend biopsy for confirmation. The specificity of DGP IgA/IgG^[6](#fhir-question-d21c275f96d617ea3cc35e85c22405f6),[7](#fhir-question-adfb960c4dcb1fbf6bd7cf3e6e5947e1)^ or TTG-IgG^[8](#fhir-question-cc6c1990892516843f18671f7ec0288f),[9](#fhir-question-b46f48b15432c0b1a05cfe2d6d41d1c2)^ for celiac disease is suboptimal when compared with TTG-IgA (REF). Empiric treatment for celiac disease under these circumstances without tissue confirmation is typically not advised, even in the presence of symptoms and presence of a celiac disease risk gene. Potential drawbacks of forgoing a biopsy should be thoroughly discussed (including erroneous celiac disease diagnosis, missed conditions, adherence implications of the lack of biopsy confirmation, management dilemmas in the event that the symptoms return or do not completely dissipate).

### No, my patient is IgA sufficient, TTG-IgA is negative, but deamidated gliadin IgA or IgG OR tissue transglutaminase IgG is elevated
Cannot make a serologic diagnosis of celiac disease. Would otherwise recommend biopsy. The specificity of DGP IgA/IgG^[6](#fhir-question-d21c275f96d617ea3cc35e85c22405f6),[7](#fhir-question-adfb960c4dcb1fbf6bd7cf3e6e5947e1)^ or TTG-IgG^[8](#fhir-question-cc6c1990892516843f18671f7ec0288f),[9](#fhir-question-b46f48b15432c0b1a05cfe2d6d41d1c2)^ for celiac disease is suboptimal when compared with TTG-IgA (REF). Empiric treatment for celiac disease under these circumstances without tissue confirmation is typically not advised, even in the presence of symptoms and presence of a celiac disease risk gene. Potential drawbacks of forgoing a biopsy should be thoroughly discussed (including erroneous celiac disease diagnosis, missed conditions, adherence implications of the lack of biopsy confirmation, management dilemmas in the event that the symptoms return or do not completely dissipate).

### No, the patient is not symptomatic; testing was performed as a result of a screening protocol
Regardless of the degree of tissue transglutaminase IgA titers, it is strongly advised to biopsy-confirm the presence of celiac disease in asymptomatic children. No current guideline worldwide provides for a non-biopsy diagnosis without clear symptoms in a child and the positive predictive value of non-biopsy protocols for celiac disease potentially suffer when symptoms are lacking. Further, children with other autoimmune conditions such as inflammatory bowel disease or infections may demonstrate elevated tissue transglutaminase IgA titers in the absence of celiac disease.^[10](#fhir-question-fbf64740e8a4374404e2fb19480feefa)^ Advise parents as to potential drawbacks of forgoing a biopsy under these circumstances (erroneous celiac disease diagnosis, adherence implications of the lack of biopsy confirmation, management dilemmas in the event that the child develops new symptoms following treatment).

Medical information provided on this site has been prepared by medical professionals and reviewed by Celiac Disease Foundation’s Medical Advisory Board for accuracy. Information contained on this site should only be used with the advice of your physician or health care professional.